Bosnian Journal of Basic Medical Sciences (BJBMS)
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Development and validation of the competing risk nomogram and risk classification system for predicting cancer-specific mortality in patients with cervical adenosquamous carcinoma treated via radical hysterectomy
In this study, we established and validated a competing risk nomogram for predicting the cumulative incidence of cervical adenosquamous carcinoma (ASC)-specific death in patients undergoing radical hysterectomy. Patients diagnosed with ASC between 2010 and 2019 were retrieved from the Surveillance, Epidemiology, and End Results database. The cumulative incidence function for various variables influencing ASC-specific mortality was computed. A Fine–Gray competing risk model was used to identify independent predictors, formulating a competing risk nomogram. A multivariate Cox proportional hazards model was also applied for comparative analysis. The performance of the nomogram was assessed using metrics, such as the concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis. A corresponding risk classification system was constructed based on nomogram-derived scores. Factors, such as advanced age, racial background (Black race), higher tumor grade, increased tumor size, advanced TNM stage, and receipt of radiotherapy without chemotherapy, were found to be positively associated with elevated ASC-specific mortality. Additionally, age, T stage, M stage, and chemotherapy were identified as independent predictors correlated with ASC-specific mortality. The established nomogram exhibited accurate discriminatory capabilities and superior net benefits compared to the traditional TNM staging system. Additionally, the high-risk group consistently demonstrated higher probabilities of ASC-specific death in both the training and validation sets. The developed nomogram proficiently quantified the incidence of ASC-specific death in patients subjected to radical hysterectomy for ASC. This tool could help clinicians in formulating personalized treatment strategies and devising follow-up protocols
Beta lactam antibiotics residues in cow\u27s milk: comparison of efficacy of three screening tests used in Bosnia and Herzegovina
Beta lactam antibiotics are widely used in therapy of cattle, particularly for the treatment of mastitis. Over 95% of residue testing in dairies in Bosnia and Herzegovina is for Beta lactams. The aim of this paper is to compare the efficacy of three most common screening tests for Beta lactam residues in cow’s milk in our country. The tests used in the study are SNAP β Lactam test (Idexx), Rosa Charm β Lactam test and Inhibition MRL test. Study samples included: standardized concentrations of penicillin solution (0, 2, 3, 4, 5 and 6 ppb). In addition we tested milk samples from three equal size study groups (not receiving any antibiotic therapy, treated with Beta lactams for mastitis and treated with Beta lactams for diseases other than mastitis). Sensitivity and specificity were determined for each test, using standard penicillin concentrations with threshold value set at concentration of 4 ppb (Maximum residue level – MLR). Additionally we determined proportions of presumably false negative and false positive results for each test using results of filed samples testing. Agreement of test results for each test pair was assessed through Kappa coefficients interpreted by Landis-Koch scale. Detection level of all tests was shown to be well below MRL. This alongside with effects of natural inhibitors in milk contributed to finding of positive results in untreated and treated animals after the withholding period. Screening tests for beta lactam residues are important tools for ensuring that milk for human consumption is free from antibiotics residues
Systemic immune-inflammation index and the short-term mortality of patients with sepsis: A meta-analysis
The systemic immune-inflammation index (SII) is a novel biomarker that reflects the balance between the host immune response and inflammation, two key pathophysiological processes involved in sepsis. This meta-analysis aimed to evaluate the relationship between SII at admission and short-term mortality in patients with sepsis. Literature searches were performed in PubMed, Embase, Web of Science, CNKI, and Wanfang up to August 30, 2024, using relevant search terms. Observational studies that reported the association between SII and short-term mortality in sepsis patients were included. Risk ratios (RRs) and 95% confidence intervals (CIs) comparing the incidence of mortality within 90 days in patients with sepsis with a high versus low SII were calculated. Nine cohort studies, with a total of 25,626 patients, were included. A high SII at admission was significantly associated with an increased risk of all-cause short-term mortality in sepsis patients (RR: 1.51, 95% CI: 1.31–1.67, P < 0.001), with moderate heterogeneity (I² = 43%). Sensitivity analyses confirmed the robustness of these findings. Subgroup analyses suggested a stronger association in patients younger than 67 years compared to those aged 67 years or older (P = 0.04), but no significant differences were observed based on sex, SII cutoff values, or follow-up duration. In conclusion, this meta-analysis demonstrates that elevated SII at admission is associated with an increased risk of short-term mortality in sepsis patients, particularly in younger individuals. Further research is needed to validate these findings and explore their clinical implications
Preventive effects of sodium hyaluronate combined with pelvic floor neuromuscular electrical stimulation on the intrauterine adhesions in women after abortion
The aim of this study was to investigate the clinical efficacy of combining pelvic floor neuromuscular stimulation treatment (NMES) with sodium hyaluronate in preventing intrauterine adhesions (IUA) following abortion. A total of 140 women who underwent artificial abortion were enrolled. The control group received only an intrauterine injection of sodium hyaluronate post-surgery, while the observation group received both the injection and daily pelvic floor NMES treatments, beginning on the day after the abortion. Monthly follow-ups on menstrual conditions were conducted for six months post-surgery. Fasting venous blood samples from both groups were collected on the second day post-abortion and the day after treatment. Transvaginal color Doppler ultrasound was used on the second day post-abortion and the 15th day post the first menstrual cycle to measure endometrial thickness, and the pulsatility and resistance indices of the endometrial spiral arteries. Over the six-month follow-up, the combination therapy group exhibited a notably lower IUA incidence compared to the control group (2.8% vs. 15.7%). Furthermore, combined treatment significantly expedited post-abortion menstrual recovery, reduced vaginal bleeding volume and duration (P < 0.001). It also increased endometrial thickness and reduced the endometrial spiral artery\u27s pulsatility and resistance indices (P < 0.05). In addition, lower serum tumor necrosis factor alpha (TNF-α) and higher interleukin-10 (IL-10) were found in the observation group compared to the control group (P < 0.05). The combination therapy offers significant advantages in preventing and reducing IUA after abortion, resulting in a substantial reduction in IUA occurrence
Stem cell therapy for degenerative disc disease: Bridging the gap between preclinical promise and clinical potential
Stem cell therapy has gained attention in the field of regenerative medicine due to its potential to restore damaged tissue. This article focuses on the application of stem cell therapy for treating spinal pathologies, particularly intervertebral disc degeneration. Disc degeneration is a major cause of low back pain and is characterized by changes in the matrix and inflammation. Animal studies have demonstrated that the implantation of mesenchymal stem cells (MSCs) yields promising results, including increased disc height, improved hydration, and reduced inflammation. However, the number of clinical trials remains limited, necessitating further research to optimize MSCs therapy. Although preclinical studies offer valuable insights, caution is needed when extrapolating these findings to clinical practice. Stem cell therapy still faces multiple challenges, such as the durability and survival of MSCs upon implantation, uncertain pathways to discogenic differentiation, and the adverse impact of a harsh microenvironment on cell survival. The avascular nature of the intervertebral disc and dynamic loading conditions also affect the adaptation of transplanted cells. Despite these obstacles, stem cell therapy holds promise as a potential treatment for disc degeneration, and ongoing research aims to fill the current gap in conclusive data
ELANE rs17223045C/T and rs3761007G/A variants: Protective factors against COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for causing coronavirus disease 2019 (COVID-19). The development and severity of this infectious disease is influenced by a combination of environmental and genetic factors. Angiotensin-converting enzyme 2 (ACE2) facilitates SARS-CoV-2 entry into human cells, with transmembrane serine protease 2 (TMPRSS2) playing a crucial role in S protein priming. Other proteases, such as cathepsin L and elastase, neutrophil-expressed (ELANE), have the capability to prime the S protein and contribute to SARS-CoV-2 infection. ELANE variants have not been previously examined in COVID-19 patients. We aimed to assess the association of single nucleotide variants (SNVs) within ELANE with COVID-19 and biochemical markers. The study included 319 SARS-CoV-2-infected patients and 288 controls. Genotyping of ELANE rs17216663C/T (Pro257Leu), rs17223045C/T (As1n30Asn), and rs3761007G/A was conducted using a 5\u27-nuclease allelic discrimination assay (TaqMan assay). Our findings indicate that ELANE rs17223045C/T (C vs T: odds ratio [OR] 0.08, P = 0.005, and CC vs CT: OR 0.08, P = 0.005) and rs3761007G/A (G vs A: OR 0.38, P = 0.009, and GG vs GA: OR 0.40, P = 0.008) confer protection against COVID-19. However, these variants were not associated with biochemical markers. In conclusion, our data suggests that ELANE rs17223045C/T and rs3761007G/A SNVs may play a protective role against COVID-19
Risk and prognosis of second cutaneous melanoma after radiotherapy for breast cancer: A population-based analysis
Radiation therapy (RT), a primary treatment for breast cancer (BC), may be associated with increased non-BC tumor risk. We aimed to examine second cutaneous melanoma (SCM) risk in BC patients who underwent RT and to assess their survival outcomes. Data from 520,977 BC patients diagnosed between 1973–2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative SCM incidence was estimated using the Fine–Gray competing risk model. Poisson regression analysis was conducted to calculate the standardized incidence ratio (SIR) and estimate the SCM relative risk in patients who underwent RT compared to those who did not. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan‒Meier method. Among the 520,977 BC patients, 243,676 (46.8%) underwent surgery and RT, while 277,301 (53.2%) only underwent surgery. Our results suggest that BC patients receiving RT had a higher SCM risk than those who did not (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.30-1.51; P < 0.001). SCM incidence was also higher in BC patients treated with RT than in the general US population (SIR 1.12; 95% CI 1.05-1.19; P < 0.05). However, SCM patients who received RT had a significantly higher 10-year survival rate than those who did not receive RT (14.90% vs 5.94%; P < 0.001). No significant difference was found in 10-year OS or 5-year CSS between SCM following RT and only primary cutaneous melanoma (OPCM), but SCM patients who did not receive RT had a significantly lower 10-year OS, with no significant difference in CSS. This study suggests an increased SCM likelihood in BC patients due to RT, although the overall risk is minimal
SPDEF drives pancreatic adenocarcinoma progression via transcriptional upregulation of S100A16 and activation of the PI3K/AKT signaling pathway
Pancreatic adenocarcinoma (PAAD) is a notably aggressive malignancy with limited treatment options and an unfavorable prognosis for patients. We aimed to investigate molecular mechanisms by which Sam\u27s pointed domain-containing ETS transcription factor (SPDEF) exerts effects on PAAD progression. We analyzed differentially expressed genes (DEGs) and their integration with ETS family members using the The Cancer Genome Atlas (TCGA) database, hence identifying SPDEF as a core gene in PAAD. Kaplan-Meier survival analysis confirmed SPDEF’s prognostic potential. In vitro experiments validated the association with cell proliferation and apoptosis, affecting pancreatic cancer cell dynamics. We detected increased SPDEF expression in PAAD tumor samples. Our in vitro studies revealed that SPDEF regulates mRNA and protein expression levels, and significantly affects cell proliferation. Moreover, SPDEF was associated with reduced apoptosis and enhanced cell migration and invasion. In-depth analysis of SPDEF-targeted genes revealed four crucial genes for advanced prognostic model, among which S100A16 was significantly correlated with SPDEF. Mechanistic analysis showed that SPDEF enhances the transcription of S100A16, which in turn enhances PAAD cell migration, proliferation, and invasion by activating the PI3K/AKT signaling pathway. Our study revealed the critical role of SPDEF in promoting PAAD by upregulating S100A16 transcription and stimulating the PI3K/AKT signaling pathway. This knowledge deepened our understanding of pancreatic cancer\u27s molecular progression and unveiled potential therapeutic strategies targeting SPDEF-driven pathways
Effects of intermittent overload doses of oral vitamin D3 on serum 25(OH)D concentrations and the incidence rates of fractures, falls, and mortality in elderly individuals: A systematic review and meta-analysis
Vitamin D is commonly used to prevent and treat osteoporosis, with studies indicating its potential to reduce fractures, falls, and mortality. However, meta-analyses present inconsistent findings regarding its efficacy, particularly reflecting significant variability in data and outcomes related to various dosing regimens. In this meta-analysis, we assessed the impact of high-dose intermittent oral administration of vitamin D3 on serum 25(OH)D levels, fractures, falls, and mortality among elderly individuals. We included 14 randomized controlled trials (RCTs) and employed Review Manager 5.4 for statistical analysis. Our findings indicate that intermittent monthly administration of vitamin D3 (over 800 IU per day) significantly raised serum 25(OH)D levels at all timepoints after six months, maintaining levels above 75 nmol/L throughout the year. This regimen showed no increase in all-cause mortality, with a risk ratio (95% CI) of 0.95 (0.87-1.04). Likewise, it did not significantly reduce the risks of falls and fractures, with risk ratios of 1.02 (0.98-1.05) and 0.95 (0.87-1.04) respectively. Although one-year intermittent administration significantly increased the concentration of 25(OH)D in serum, further research is needed to determine if this method would increase the incidence of falls. Therefore, it is not recommended at this stage due to the lack of demonstrated safety in additional relevant RCTs. This study had been registered at PROSPERO (CRD42022363229)
Predictive and prognostic value of preoperative pan-immune-inflammation value in patients with locally advanced rectal cancer
This study aimed to investigate the prognostic value of the pan-immune-inflammation value (PIV) in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision. We retrospectively collected and analyzed the clinicopathological data of 215 resected LARC patients. X-tile software was used to determine the optimal threshold value for PIV in predicting overall survival (OS). The predictive ability of PIV for pathological complete regression (pCR), OS, and disease-free survival (DFS) was evaluated and compared with other inflammation markers. Univariate and multivariate logistic regression analyses for pCR and Cox regression analyses for OS and DFS were conducted. The optimal threshold value for PIV was determined to be 454.7 based on the X-tile software. Patients were then categorized into low (≤ 454.7) and high (> 454.7) PIV groups comprising 153 and 62 patients, respectively. PIV demonstrated superior predictive ability for pCR, OS, and DFS compared to other inflammation markers. LARC patients with low PIV had significantly higher pCR (P = 0.029), OS (P = 0.002), and DFS (P = 0.001) rates compared to those with high PIV. Multivariate regression analysis identified PIV as an independent prognostic factor for pCR (odds ratio = 0.32; 95% confidence interval [CI], 0.10-0.80; P = 0.014), OS (hazard ratio = 3.08; 95% CI, 1.77-5.35; P = 0.001), and DFS (hazard ratio = 2.53; 95% CI, 1.58-4.06; P = 0.002). This study confirmed that preoperative PIV could serve as a useful independent prognostic factor in LARC patients treated with nCRT